Medical treatment of some illnesses requires continuous drug infusion into various body compartments, such as subcutaneous and intra-venous injections. Diabetes mellitus patients, for example, require administration of varying amounts of insulin throughout the day to control their blood glucose levels. In recent years, ambulatory portable insulin infusion pumps have emerged as a superior alternative to multiple daily syringe injections of insulin. These pumps, which deliver insulin at a continuous basal rate as well as in bolus volumes, were developed to liberate patients from repeated self-administered injections, and enable them to maintain a near-normal daily routine. Both basal and bolus volumes generally have to be delivered in relatively precise doses, according to an individual prescription, since an overdose or under-dose of insulin could be fatal.
Several ambulatory insulin infusion devices are currently available on the market. Mostly, these devices comprise a housing containing a driving mechanism, a power source, a controller, electronics and other minor components. Such devices generally include a disposable reservoir, configured as a conventional syringe containing insulin, which is received within the housing, and which is replaced every 2-3 days of operation. A disposable infusion set, which includes a distally located needle/cannula assembly including a cannula and a penetrating member, is connected to the reservoir at its proximal end via a fluid communication tube. Usually, the patient fills the syringe with insulin, attaches the infusion set to an exit port of the syringe, and then inserts the syringe into the pump. After purging air out of the syringe and infusion set, the patient subcutaneously inserts the penetrating member and cannula, at a selected location on the body, and withdraws the penetrating member. To avoid irritation and infection, the subcutaneously inserted cannula must be replaced and discarded after 2-3 days, together with the empty syringe. The syringe plunger is driven by a driving mechanism which includes a threaded-rod (also referred to as a “threaded plunger rod” or “threaded piston rod”), a motor, and controller/electronics. Examples of first generation syringe-type dispensing mechanism are described, for example, in U.S. Pat. No. 3,631,847 to Hobbs, U.S. Pat. No. 3,771,694 to Kaminski, U.S. Pat. No. 4,657,486 to Stempfle, and U.S. Pat. No. 4,544,369 to Skakoon, the contents of all of which are hereby incorporated by reference in their entireties. Other dispensing mechanisms have been also discussed, including peristaltic positive displacement pumps, as described, for example, in U.S. Pat. No. 4,498,843 to Schneider and U.S. Pat. No. 4,715,786 to Wolff, the contents of all of which are hereby incorporated by reference in their entireties.
Although these devices represent an improvement over multiple daily injections, they nevertheless all suffer from several drawbacks. One drawback is the large size and weight of the devices, caused by the configuration and the relatively large size of the driving mechanism and syringe. These relatively bulky devices have to be regularly carried in a patient's pocket or attached to his/her belt. Consequently, the fluid delivery tube of the infusion set is very long, usually greater than 60 cm, in order to enable needle/cannula insertion at remote sites of the body. These uncomfortable, bulky devices and long infusion sets are disfavored by the majority of diabetic insulin users, since they disturb regular activities, such as sleeping and swimming. Furthermore, the effect of the image projected on the teenagers' body is unacceptable. In addition, the use of a delivery tube excludes some standard remote insertion sites, like buttocks, arms and legs.
To avoid the noted consequences of a long delivery tube of the infusion set, a new concept of second generation pumps was proposed. This concept included a remote controlled skin securable (e.g., adherable) device with a housing having a bottom surface adapted to contact patient's skin, a reservoir disposed within the housing, and an injection needle adapted to communicate with the reservoir. These skin adherable devices are disposed of every 2-3 days (similarly to other available pump infusion sets). These devices are described, for example, in U.S. Pat. No. 5,957,895 to Sage, U.S. Pat. No. 6,589,229 to Connelly, and U.S. Pat. No. 6,740,059 to Flaherty, the contents of all of which are hereby incorporated by reference in their entireties. Additional configurations of skin securable pumps are described in U.S. Pat. No. 6,723,072 to Flaherty and U.S. Pat. No. 6,485,461 to Mason, the contents of all of which are hereby incorporated by reference in their entireties.
Second generation skin adherable infusion devices suffer from major drawbacks which include, inter alia, the following:                They are heavy and bulky because:                    The syringe-type reservoir is cylindrical in shape and therefore, if the devices require retaining, for example, 3 ml of deliverable drug, their dimensions are such that they are either long with a small diameter (e.g., 60 mm long, 8 mm inner diameter) or short with large diameter (e.g., 17 mm long, 15 mm inner diameter). These devices' dimensions can result in considerable discomfort to the patient while the device is adhered to his/her skin.                        The cannula insertion mechanism is contained within the housing of the device. Thus, the user has to carry this mechanism (generally a bulky spring loaded mechanism) during the 2-3 operating period of the devices.        The energy supplied generally requires more than one battery, e.g., four batteries.        The costs of using second generation devices is generally high because the entire device, including the relatively expensive components (electronics, driving mechanism, etc.), has to be disposed of every 3 days or so.        Reservoir filling requires an additional syringe to draw the fluid from a container (e.g., a glass bottle) to fill the pump reservoir. This procedure is cumbersome and the risk of accidental piercing by the syringe needle is high.        Second generation devices generally cannot be disconnected from the patient's body, although there are situations in which patients would prefer to temporarily disconnect the pump (e.g., while taking showers, while participating in sports activities, etc.).        The cannula is rigidly secured to the pump housing, and consequently users typically cannot choose cannula length and/or vary the insertion angle.        Insulin wastage—In the event of site-misplacement of the cannula (because of scarred tissue, bleeding, cannula kinking, etc.) the entire device, including the filled insulin reservoir, has to be disposed of.        Device controlling—available wirelessly-controlled pumps do not provide the user with the ability to control the delivery of insulin without the remote control. This can be dangerous in the event the user loses his/her remote control, and may also result in the creation of psychological barriers for the user to trust the pump's operation.        
To mitigate the costs issues associated with second-generation devices, and to improve patient's customization of the configuration, functionality and features of their devices, a third generation of skin securable (e.g., adherable) dispensing device was proposed and developed. An example of such a device is described in co-pending/co-owned U.S. patent application Ser. No. 11/397,115 and International Patent Application No. PCT/IL06/001276, the contents of which are hereby incorporated by reference in their entireties. In a third generation device, a dispensing unit is employed, which is composed of two parts: a reusable part, that includes a driving mechanism, electronics, and other relatively expensive components, and a disposable part that includes relatively inexpensive components, such as, for example, a reservoir, a power source (which may form part of the reusable and/or the disposable part, or may be a separate component), etc.
A third generation device provides a more cost-effective solution and enables diverse use of the device. An improvement to a third generation skin securable pump that includes two parts (e.g., a reusable part and a disposable part) is described, for example, in co-pending/co-owned U.S. patent application Ser. No. 12/004,837 and International Patent Application No. PCT/IL07/001,578, the contents of which are hereby incorporated by reference in their entireties. These disclosures include embodiments directed to a device and a method for connection and disconnection of a skin adherable dispensing unit. In some such embodiments, the device includes a cradle unit which is initially adhered to the skin. A cannula is then inserted through the cradle unit into the body of the user. Insertion can be done automatically by a designated inserter, or may be done manually. The dispensing unit of the device can also be connected and disconnected to and from the skin-adhered cradle at the patient's discretion. This concept enables versatile operational modes that include manual and automatic cannula insertion, use of cannulae with various lengths, and also enables cannula insertion at various insertion angles. The cradle is disposable and relatively inexpensive, and may be discarded every 2-3 days. Unlike second generation infusion pumps, in the event of site misplacement of the cannula (due to scarred tissue, bleeding, cannula kinking, etc.) only the cradle and cannula need to be disposed of and replaced, rather than the whole device. Consequently, under those circumstances, the reservoir, still containing unused insulin, can be used when the infusion device is connected to a new cradle/cannula arrangement.
Currently available third generation devices nevertheless have a few drawbacks, including:                Waste of insulin—the disposable reservoir has to be filled to its full capacity, and thus, in situations where the user used less than the full capacity of insulin, some insulin will be discarded (e.g., during three days of operation a user consumes 1 nil, corresponding to 100 Insulin Units, from the available 2 ml in the reservoir, corresponding to 200 IU of insulin, resulting in a waste of 1 ml of insulin)        Reservoir volume cannot be precisely monitored and a “low volume” alert is generally not available.        Filling process requires an accessory syringe to draw insulin from another container (e.g., a vial) to fill the reservoir.        Complexity of components.        Relatively high cost of manufacturing currently available third-generation devices.        